PROPOFOL PRODUCES ENDOTHELIUM-INDEPENDENT VASODILATION AND MAY ACT ASA CA2+ CHANNEL BLOCKER

The mechanism of vasodilation induced by propofol was investigated usi ng isolated rat thoracic aortic rings. Aortic rings were precontracted with potassium chloride (KCl) (40 mM) or phenylephrine (PE) (3 X 10(- 8) to 3 X 10(-7) M) in the presence and absence of intact endothelium. Propofol produced similar concentration-dependent relaxation in aorti c rings with and without endothelium regardless of whether they were p recontracted with KCl or PE. The relaxation response to propofol was s ignificantly greater in KCl-contracted aortic rings than in PE-contrac ted aortic rings. The propofol concentration producing 50% relaxation from the contracted state (RC50) was lower in aortic rings contracted with KCl than with PE, both with (5 +/- 0.6 X 10(-5) M vs 8.3 +/- 5.7 X 10(-4) M, P < 0.001) and without intact endothelium (3.9 +/- 0.5 X 1 0(-5) M vs 7.2 +/- 3.8 X 10(-4) M, p < 0.001). Propofol inhibited the Ca2+-induced contractions of aortic rings exposed to Ca2+-free media a nd depolarized with KCl (40 mM, 100 mM) in a dose-dependent manner. Th ese effects are similar to those produced by verapamil. Propofol (5 X 10(-5) M) had minimal effect on the intracellular Ca2+ release elicite d by PE (10(-5) M). We conclude that vasodilation produced by propofol is not endothelium-dependent but is likely due to blockade of voltage -gated influx of extracellular Ca2+.